Description of Research
Our lab is focused on the molecular pathways involved in the formation and differentiation of the mammalian lung and cardiovascular system. In the mouse, the lung develops from the primitive foregut endoderm at approximately E9.5 of gestation. Budding endoderm from the foregut differentiates into primitive pulmonary epithelium and which is surrounded by splanchnic mesoderm, which forms the lung mesenchyme. As development proceeds, cell specific programs are initiated along a proximal-distal axis such that epithelial cell lineages are distinct in the proximal versus distal regions of the lung by mid to late gestation (E15.5-E17.5). This patterning is similar to that observed in other branching organs including the kidney and mammary gland.

The cardiovascular system begins to develop at E7.5 when the precardiac mesoderm initially begins to differentiate into definitive cardiac cell lineages. Further development results into the four-chambered heart and the complex vascular plexus required for survival past early to mid gestation. Several cell types contribute to the morphogenesis of the cardiovascular system including mesodermally derived cardiac and vascular smooth musclemyocytes, neural crest derived vascular smooth muscle, and endothelium. Of these cell types, the development and differentiation of vascular smooth muscle remains relatively unexplored. We have identified several transcription factors and signaling molecules that are important for lung and cardiovascular development including the zinc finger transcription factor GATA-6, Foxp1/2/4, and the Wnt signal transduction pathway. We utilize in vivo mouse and zebrafish models to study the role of these factors during development. This includes the generation and analysis of transgenic and knock-out mice and morpholino knock-down strategies in fish. Our overall goal is to elucidate the underlying causes and mechanisms that lead to both neonatal and adult cardiopulmonary disease.

Rotation Projects for 2006-2007
General topics include:
- role of Wnt signaling in vascular and airway development
- fate mapping of vascular and epithelial stem/progenitor cells in the lung
- explore redundancy of Foxp1/2/4 in lung and cardiovascular development
- characterize novel Foxp1/2/4 interacting proteins and their role in chromatin remodeling

Zhao,R., Watt, A.J., Li,J., Luebke-Wheeler, J., Morrisey, E.E., and Duncan, S.A.: GATA6 is essential for embryonic development of the liver but dispensable for early heart development. Molecular and Cellular Biology 25(7): 2622-2631, April 2005.